Atherosclerosis 212 (2010) 607–613 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis Acute infection with Epstein–Barr virus is associated with atherogenic lipid changes F. Apostolou a , I.F. Gazi a , K. Lagos a , C.C. Tellis b , A.D. Tselepis b , E.N. Liberopoulos a , M. Elisaf a,∗ a Department of Internal Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece b Laboratory of Biochemistry, School of Chemistry, University of Ioannina, Ioannina, Greece article info Article history: Received 2 April 2010 Received in revised form 30 May 2010 Accepted 3 June 2010 Available online 11 June 2010 Keywords: Epstein–Barr virus Lipids Small-dense LDL particles Cytokines Lipoprotein-associated phospholipase A2 (Lp-PLA2) abstract Objective: To evaluate the effects of acute infection with Epstein–Barr virus (infectious mononucleosis, IM) on lipids and lipoproteins. Methods: Fasting serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high- density lipoprotein cholesterol (HDL-C), triglycerides (TGs), apolipoproteins (apo) A-I, B, E, C-II, C-III and lipoprotein (a) [Lp(a)] were determined in patients with IM on diagnosis and 4 months after the resolution of febrile illness and in age- and sex-matched controls. Activities of cholesteryl-ester transfer protein (CETP), lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) and paraoxonase 1 (PON1) as well as levels of several cytokines were determined. LDL subclass analysis was performed with the Lipoprint LDL System. Results: Twenty-nine patients (16 males, aged 24.3 ± 14.6 years) and 30 controls were included. TC, HDL-C, LDL-C, apoA-I, apoB, apoC-III and Lp(a) levels were lower at baseline whereas apoB/apoA-I ratio, TG levels and CETP activity were elevated compared with 4 months later. At baseline, higher levels in cytokines and the cholesterol concentration of small-dense LDL particles (sdLDL-C) were noticed, whereas LDL particle size was lower compared with follow-up. Activities of Lp-PLA 2 and PON1 were similar at baseline and 4 months later. Four months after the resolution of IM levels of TGs, apoE, apoC-III, Lp(a), sdLDL-C and cytokines as well as LDL particle size, apoB/apoA-I ratio, CETP and Lp-PLA 2 activities were similar to controls. PON1 activities both at baseline and 4 months later were lower in patients compared with controls. Conclusions: IM is associated with atherogenic changes of lipids and lipoproteins that are partially restored 4 months after its resolution. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Atherogenesis resembles chronic inflammation in many aspects and the atherogenetic process may be promoted by microorgan- isms [1]. Infections with chlamydia pneumoniae, cytomegalovirus (CMV), herpes simplex virus (HSV), helicobacter pylori as well as periodontitis have been mostly implicated [1]. Infection is associated with cytokine-induced changes in lipid and lipoprotein metabolism [2], such as reductions in serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL- C), low-density lipoprotein cholesterol (LDL-C), apolipoproteins (apo) A-I, B and lipoprotein (a) [Lp(a)], and increases in triglyceride (TG) and apoE concentrations [2]. Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is mainly distributed on LDL subclasses (80%), while the remaining is found on HDL (HDL-Lp-PLA 2 ) [3]. Studies have shown that an increase in ∗ Corresponding author. Tel.: +30 2651007509; fax: +30 2651007016. E-mail address: egepi@cc.uoi.gr (M. Elisaf). Lp-PLA 2 mass or activity represents an independent cardiovascular risk factor [4]. On the other hand, HDL-Lp-PLA 2 may exhibit anti- atherogenic properties [3]. Various changes in Lp-PLA 2 activity in response to infection and inflammation have been reported among different animal species [5] and in population-based studies [6,7]. Therefore, infection-induced atherogenesis could, at least in part, be mediated by alterations of Lp-PLA 2 activity. Paraoxonase 1 (PON1) is an esterase exclusively associated with HDL in plasma [8]. PON1 plays an important role in HDL-mediated anti-atherogenic action. During infection and inflammation serum PON1 activity may decrease and acute phase HDL is unable to pro- tect LDL against oxidation [9]. In addition, cholesteryl-ester transfer protein (CETP) plays a central role in the regulation of serum HDL- C levels. High CETP activity may be associated with a reduction in HDL-C levels and an atherogenic lipoprotein profile during infec- tion [10]. LDL particles consist a heterogeneous population in regard to size, composition and density [11]. Several studies have shown that small-dense LDL (sdLDL) particles are more atherogenic compared with large buoyant ones [11]. Periodontitis and human immunod- 0021-9150/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2010.06.006